The metabolism of steroids by the gut microbiome affects hormone homeostasis, impacting host development, mental health, and reproductive functions. In this study, we identify the Δ-3-ketosteroid 5β-reductase, 3β-hydroxysteroid dehydrogenase/Δ isomerase, and Δ-3-ketosteroid reductase enzyme families encoded by common human gut bacteria. Through phylogenetic reconstruction and mutagenesis, We show that 5β-reductase and Δ-3-ketosteroid reductase have evolved to specialize in converting diverse 3-keto steroid hormones into their 5β- and Δ-reduced derivatives.
View Article and Find Full Text PDFMetabolism of haem by-products such as bilirubin by humans and their gut microbiota is essential to human health, as excess serum bilirubin can cause jaundice and even neurological damage. The bacterial enzymes that reduce bilirubin to urobilinogen, a key step in this pathway, have remained unidentified. Here we used biochemical analyses and comparative genomics to identify BilR as a gut-microbiota-derived bilirubin reductase that reduces bilirubin to urobilinogen.
View Article and Find Full Text PDFThe D7 proteins are highly expressed in the saliva of hematophagous Nematocera and bind biogenic amines and eicosanoid compounds produced by the host during blood feeding. These proteins are encoded by gene clusters expressing forms having one or two odorant-binding protein-like domains. Here we examine functional diversity within the D7 group in the genus Anopheles and make structural comparisons with D7 proteins from culicine mosquitoes in order to understand aspects of D7 functional evolution.
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